The DOI matches its Crossref record; 41 of the 42 references it cites were found in a registry or an index.
AXL Mediates Resistance to PI3Kα Inhibition by Activating the EGFR/PKC/mTOR Axis in Head and Neck and Esophageal Squamous Cell Carcinomas
Open accessAbstract
Phosphoinositide-3-kinase (PI3K)-α inhibitors have shown clinical activity in squamous cell carcinomas (SCCs) of head and neck (H&N) bearing PIK3CA mutations or amplification. Studying models of therapeutic resistance, we have observed that SCC cells that become refractory to PI3Kα inhibition maintain PI3K-independent activation of the mammalian target of rapamycin (mTOR). This persistent mTOR activation is mediated by the tyrosine kinase receptor AXL. AXL is overexpressed in resistant tumors from both laboratory models and patients treated with the PI3Kα inhibitor BYL719. AXL dimerizes with and phosphorylates epidermal growth factor receptor (EGFR), resulting in activation of phospholipase Cγ (PLCγ)-protein kinase C (PKC), which, in turn, activates mTOR. Combined treatment with PI3Kα and either EGFR, AXL, or PKC inhibitors reverts this resistance.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“AXL inhibition has been reported to sensitize drug-resistant mesenchymal tumor cells to anticancer agents, including antimitotic agents, epidermal growth factor receptor (EGFR) inhibitors, and PI3K inhibitors”
From Hypoxic control of metastasis (2016) · cites this paper as [85]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Jemal, A., Bray, F., Ferlay, J., Ward, E., & Forman, D. (2011) · CA A Cancer Journal for Clinicians · doi:10.3322/caac.20107 · Cited by 55,044
Cerami, E., Gao, J., Dogrusoz, U., Gross, B. E., Sumer, S. O., Aksoy, B. A., Jacobsen, A., Byrne, C. J., Heuer, M. L., Larsson, E., et al. (2012) · Cancer Discovery · doi:10.1158/2159-8290.cd-12-0095 · Cited by 17,455
The phosphatidylinositol 3-Kinase–AKT pathway in human cancer
Vivanco, I., & Sawyers, C. L. (2002) · Nature reviews. Cancer · doi:10.1038/nrc839 · Cited by 6,155
Radiotherapy plus Cetuximab for Squamous-Cell Carcinoma of the Head and Neck
Bonner, J. A., Harari, P. M., Giralt, J., Azarnia, N., Shin, D. M., Cohen, R. B., Jones, C. U., Sur, R. K., Raben, D., Jassem, J., et al. (2006) · New England Journal of Medicine · doi:10.1056/nejmoa053422 · Cited by 5,109
Self-citationPlatinum-Based Chemotherapy plus Cetuximab in Head and Neck Cancer
Vermorken, J. B., Mesia, R., Rivera, F., Remenar, E., Kawecki, A., Rottey, S., Erfan, J., Zabolotnyy, D., Kienzer, H.-R., Cupissol, D., et al. (2008) · New England Journal of Medicine · doi:10.1056/nejmoa0802656 · Cited by 3,726
Kamangar, F., Dores, G. M., & Anderson, W. F. (2006) · Journal of Clinical Oncology · doi:10.1200/jco.2005.05.2308 · Cited by 3,434
The Mutational Landscape of Head and Neck Squamous Cell Carcinoma
Stransky, N., Egloff, A. M., Tward, A. D., Kostic, A. D., Cibulskis, K., Sivachenko, A., Kryukov, G. V., Lawrence, M. S., Sougnez, C. L., McKenna, A., et al. (2011) · Science · doi:10.1126/science.1208130 · Cited by 2,541
Targeting PI3K signalling in cancer: opportunities, challenges and limitations
Engelman, J. A. (2009) · Nature Reviews Cancer · doi:10.1038/nrc2664 · Cited by 2,445
Exploiting the PI3K/AKT Pathway for Cancer Drug Discovery
Hennessy, B. T., Smith, D. L., Ram, P. T., Lu, Y., & Mills, G. B. (2005) · Nature Reviews Drug Discovery · doi:10.1038/nrd1902 · Cited by 2,214
Tumour micro-environment elicits innate resistance to RAF inhibitors through HGF secretion
Straussman, R., Morikawa, T., Shee, K., Barzily-Rokni, M., Qian, Z. R., Du, J., Davis, A., Mongare, M. M., Gould, J., Frederick, D. T., et al. (2012) · Nature · doi:10.1038/nature11183 · Cited by 1,771
Cited by
Sorted by citations
Head and neck squamous cell carcinoma
Johnson, D. E., Burtness, B. A., Leemans, C. R., Lui, V. W. Y., Bauman, J. E., & Grandis, J. R. (2020) · Nature Reviews Disease Primers · doi:10.1038/s41572-020-00224-3 · Cited by 4,458
Rankin, E. B., & Giaccia, A. J. (2016) · Science · doi:10.1126/science.aaf4405 · Cited by 1,340
The PI3K/AKT Pathway as a Target for Cancer Treatment
Mayer, I. A., & Arteaga, C. L. (2015) · Annual Review of Medicine · doi:10.1146/annurev-med-062913-051343 · Cited by 833
Immunosuppressive cells in cancer: mechanisms and potential therapeutic targets
Tie, Y., Tang, F., Wei, Y.-Q., & Wei, X.-W. (2022) · Journal of Hematology & Oncology · doi:10.1186/s13045-022-01282-8 · Cited by 591
Baselga, J. M., Im, S., Iwata, H., Cortés, J., Laurentiis, M. D., Jiang, Z., Arteaga, C. L., Jonat, W., Clemons, M. J., Ito, Y., et al. (2017) · The Lancet Oncology · doi:10.1016/s1470-2045(17)30376-5 · Cited by 538
Self-citation
Metadata
- Authors
- Elkabets, M., Pazarentzos, E., Juric, D., Sheng, Q., Pelossof, R. A., Brook, S., Benzaken, A. O., Rodon, J., Morse, N., Yan, J. J., Liu, M., Das, R., Chen, Y., Tam, A., Wang, H., Liang, J., Gurski, J. M., Kerr, D. A., Rosell, R., Teixidó, C., Huang, A., Ghossein, R. A., Rosen, N., Bivona, T. G., Scaltriti, M., & Baselga, J.
- Affiliations
- Memorial Sloan Kettering Cancer Center (US)
- University of California, San Francisco (US)
- Massachusetts General Hospital (US)
- Vall d'Hebron Institute of Oncology (ES)
- Hospital Universitario Dexeus (ES)
- Corresponding author
- Scaltriti, Maurizio
- ORCID
- Venue
- Cancer Cell
- Publisher
- Elsevier BV
- Published
- 2015-04
- Volume
- 27
- Issue
- 4
- Pages
- 533-546
- ISSN
- 1535-6108 (ISSN-L)
- PMC
- PMC4398915
- OpenAlex
- W2039071845
- Cited by
- 325
- References
- 42
- Citations by year
- 2026: 4 · 2025: 18 · 2024: 31 · 2023: 27 · 2022: 36 · 2021: 28 · 2020: 36 · 2019: 34 · 2018: 31 · 2017: 29 · 2016: 41 · 2015: 8
- FWCI
- 15.93
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cancer Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- Memorial Sloan-Kettering Cancer Center
- Soochow University
- National Cancer Institute (R01CA169338, DP2CA174497, P30CA008748, K12CA087723, T32CA071345)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Keywords
- AXL receptor tyrosine kinase, EGFR, protein kinase C, mTOR signaling, head and neck squamous cell carcinoma, esophageal squamous cell carcinoma, PIK3CA mutation, alpelisib, phospholipase C-gamma, combination therapy, treatment resistance
- MeSH terms
- Cetuximab, Esophageal Squamous Cell Carcinoma, Phosphoinositide-3 Kinase Inhibitors, Axl Receptor Tyrosine Kinase, Animals, Carcinoma, Squamous Cell, Esophageal Neoplasms, Head and Neck Neoplasms, Humans, Protein Kinase C, Proto-Oncogene Proteins, Thiazoles, Signal Transduction, Drug Resistance, Neoplasm, Phosphatidylinositol 3-Kinases, Receptor Protein-Tyrosine Kinases, Xenograft Model Antitumor Assays, Cell Line, Tumor, Protein Kinase Inhibitors, Mice, Class I Phosphatidylinositol 3-Kinases, TOR Serine-Threonine Kinases, Antibodies, Monoclonal, Humanized
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
